摘要：

目的 总结短链脂酰辅酶A 脱氢酶缺陷综合征临床表型和基因突变特点。方法与结果 女婴患儿，1 个月14 d，临床表现为智力和运动发育迟滞、肌张力下降、癫痫发作，发作类型为痉挛发作和全面性强直发作；体格检查可见左侧面部和左上腹部咖啡牛奶斑；尿液乙基丙二酸、甲基琥珀酸和全血丁酰肉碱水平升高；发作间期视频脑电图可见爆发-抑制波形；头部MRI显示，左侧大脑半球和右侧额叶皮质发育畸形；基因检测显示，患儿存在ACADS 基因c.795 + 1G > A 纯合突变，分别来自携带该位点杂合突变的父母。患儿明确诊断为短链脂酰辅酶A 脱氢酶缺陷综合征，该家系明确诊断为短链脂酰辅酶A脱氢酶缺陷综合征家系。在服用泼尼松4 mg/（kg·d）和左乙拉西坦30 mg/（kg·d）基础上，增加维生素B₂10 mg/（kg·d）口服。随访至今，未再出现癫痫发作。结论 短链脂酰辅酶A 脱氢酶缺陷综合征临床表现为智力和运动发育迟滞、肌张力下降和早发性癫痫性脑病，尿液乙基丙二酸、甲基琥珀酸和全血丁酰肉碱升高，并可能导致皮质发育畸形。ACADS 基因c.795 + 1G > A 纯合突变可以致病，为首次报道。

关键词: 氨基酸代谢障碍, 先天性, 表型, 基因, 突变, 系谱

Abstract:

Objective To analyze the clinical phenotype and genetic characteristics of short-chain acyl-coenzyme A dehydrogenase deficiency (SCADD). Methods and Results The proband was one month and 14 days old girl, who presented mental and motor retardation, hypotonia and epileptic seizures (convulsive seizures and generalized tonic seizures). Physical examination showed café-au-lait-spot on her left face and left upper abdomen. Ethylmalonic acid and methylsuccinic acid in urine and butyryl carnitine in whole blood were elevated. Inter-ictal discharges in video electroencephalogram (VEEG) showed burst- suppression wave. Cranial MRI demonstrated multiple cortical malformations in the left cerebral hemisphere and right frontal lobe. Genetic test showed the patient had c.795 + 1G > A homozygous mutation of ACADS gene inherited from asymptomatic parents who carried heterozygous mutations in the same locus. The patient was clearly diagnosed as SCADD, and her family was diagnosed as SCADD pedigree. The patient was treated by prednisone [4 mg/(kg·d)] and levetiracetam [30 mg/(kg·d)], and then oral vitamin B₂ [10 mg/(kg·d)] was added. No seizures recurred as yet. Conclusions Clinical manifestations of SCADD include mental and motor retardation, hypotonia, early-onset epileptic encephalopathy, elevated ethylmalonic acid, methylsuccinic acid in urine and butyryl carnitine in whole blood, and it might result in cortical malformations. The homozygous mutation c.795 + 1G > A of ACADS gene was pathogenetic, and was reported for the first time.

Key words: Amino acid metabolism, inborn errors, Phenotype, Genes, Mutation, Pedigree